Gelatin-Based Hydrogels Blended with Gellan as an Injectable Wound Dressing

Abstract

Injectable scaffolds are of great interests for skin regeneration because they can fill irregularly shaped defects through minimally invasive surgical treatments. In this study, an injectable hydrogel from biopolymers is developed and its application as wound dressings is examined. Gelatin-based hydrogels were successfully prepared at body temperature upon blending with low content of gellan, and the synergetic effect on the gel formation was carefully characterized through rheological methods. The electrostatic complexation between gelatin and gellan was confirmed to contribute a continuous hydrogel network. The obtained blend hydrogel demonstrates remarkable shear-thinning and self-recovering properties. For antibacterial purpose, tannic acid was incorporated into the blend hydrogel. In addition, tannic acid-loaded blend hydrogel was verified to accelerate the wound healing on the mice model, significantly than the control groups. Thus, this paper presents a facile approach without chemical modification to construct injectable gelatin-based hydrogels, which have great potential as a wound dressing or tissue scaffold at body temperature.

Figure 1

Gelation kinetic (A) and the viscoelastic behavior as a function of frequency (B) of blend hydrogels at 37 °C by rheological measurement. The inset is the image of blend hydrogel at 37 °C.

Figure 2

Effect of gellan on G′ (solid symbols) and G″ (open symbols) as a function of temperature at a frequency of 1.0 Hz, strain of 0.1%, and a heating rate of 1.0 °C/min.

Figure 3

Rheological measurements of blend hydrogel. (A) Viscosity of the blend hydrogel as a function of shear rate at 25 °C. Inset photograph is the patterns of blend hydrogel after injection by a 26-G syringe. The storage and loss moduli of blend hydrogel by continuous- (B) and alternate-step strain sweep (C, D) at 37 °C.

Figure 4

FTIR spectra of gelatin (a), gellan (b), and blend hydrogels (c).

Figure 5

ζ-Potentials of gelatin and gellan as a function of pH.

Figure 6

SEM image of the blend hydrogel.

Figure 7

(A) Photographs of agar diffusion test result for TA and TA-loaded blend hydrogel (5 mg/mL) against E. coli, S. aureus, and MRSA; the dotted circles depict the original size of TA-loaded filter paper or blend hydrogel. (B) The diameter of inhibition zone for TA and TA-loaded hydrogel against E. coli, S. aureus, and MRSA.

Figure 8

TA-loaded blend hydrogel promotes wound healing in a Balb/c mouse model. (A) Representative images of wound closure during 12 day experiments. Quantification of wound closure (B) and body weight (C) of mice during the treatment.

Figure 9

H&E (A) and Masson’s trichrome (B) staining, thickness of epidermis (C), and collagen content (D) of TA-loaded hydrogel group at 12 day wound healing.

Figure 10

Cell migration assay of blend hydrogel for 0, 12, and 24 h. The dotted lines indicate the wound scratch created using a pipette tip.